NEW YORK—Daxor Corp. announced in August the publication of an investigator-initiated study from Duke University and The Mayo Clinic demonstrating that despite the widespread use of formula-derived estimates of plasma volume in heart failure patients, these methods are inaccurate compared to measured volume. The study, “Calculated Estimates of Plasma Volume in Patients With Chronic Heart Failure—Comparison With Measured Volumes,” featured the company’s BVA-100 blood volume measurement diagnostic and was published in the Journal of Cardiac Failure.

“[I]ndirect assessments of plasma volume or blood volume are limited by their inaccuracy. Our study shows that this is true for formula-based volume assessment or the measure of hemoconcentration, and similarly poor correlation has previously been shown for the physical exam and even intra-cardiac pressure assessments,” said Dr. Marat Fudim, a Fellow in the Department of Cardiology at Duke University Medical Center, Duke Clinical Research Institute and one of the study authors.

According to Daxor, the BVA-100 measures total circulating blood volume and red blood cell volume in milliliters. A small tracer is injected into the patient and a series of blood samples are taken. The samples are sent to the lab for analysis, and the total time taken to administer the test and process results is about 60 minutes.

“Physicians currently rely on surrogate measures such as wedge pressure, hematocrit or formula-based estimates and imperfect clinical assessment to estimate blood volute, resulting in less accurate diagnosis and sub-optimal treatment. This matters because being able to distinguish between dilutional versus true anemia is critical in making decisions around red cell management (such as transfusions, EPO use and phlebotomy), as well as getting the patient to an overall level of total normal volume (Euvolemia),” points out a Daxor spokesperson. “The output of the BVA-100 test allows a clinician to state with certainty, for example, ‘This patient is hypervolemic, with a +30 percent total volume excess versus the patient-specific norm and a red cell deficit of -20 percent, or -656 ml.’”

“This study confirms that Daxor’s technology of direct volume measurement is of the highest clinical utility in diagnosing fluid volume overload in heart failure patients,” commented Daxor’s CEO Michael Feldschuh. “Many physicians have relied on formula-based estimates of plasma volume overload. This study quantified the very poor correlation of these calculated estimates with direct measured volume of the patients, which could potentially hinder optimal treatment and result in re-hospitalization or even death.”

Plasma volume was measured using Daxor’s BVA-100 in 110 patients with clinically stable chronic heart failure. These measurements were correlated using two different plasma volume estimation techniques. The first was the Kaplan-Hakim formula, which calculates blood volume using a formula calculating hematocrit relative to dry body weight. The second, the Strauss formula, estimates changes in plasma volume over time using hemoglobin and hematocrit measurement. The study ultimately showed neither formula demonstrated an accurate blood volume estimate compared to the BVA-100. These formulas varied in their accuracy between just 16 and 68 percent compared to Daxor’s BVA-100, the acknowledged “gold standard” of volume measurement.

“The BVA-100 utilizes a method known as the indicator tracer dilution technique,” explains the Daxor spokesperson. “Numerous studies have shown the BVA-100 methodology to be equivalent to the former gold standard dual-isotope tracer method based upon a discontinued Chromium-51 test, which was formerly the most accurate measurement of blood volume.”

“This study is further evidence showing why BVA-guided treatment of heart failure leads to significantly better results in mortality and readmission. Proxy measures such as formulas, hemodynamics and clinical assessment alone do not allow the individualization of care needed for optimal treatment of HF [heart failure]. Based on these results, we continue to work to educate physicians about direct blood volume measurement and to expand the availability of the BVA-100 across the U.S.,” said Jonathan Feldschuh, Daxor’s chief technology officer.

Daxor also recently presented two Mayo Clinic studies at the 22nd Annual Scientific Meeting of the Heart Failure Society of America in Nashville, Tenn. The studies showed that direct blood volume analysis provides doctors with important information to inform treatment, and does so at an advantage over surrogate measurements, including cardiac filling pressure and kidney function.

Notes a Daxor spokesperson, “This study is followed by a number of other studies by Miller, et al., from the Mayo Clinic, who co-authored the Journal of Cardiac Failure paper, regarding the utility and promise of direct blood volume measurement to optimize care in not only HF, but also critical care, sepsis, burn management, transfusion triggers and other areas. Clinicians have struggled to manage volume because unlike in, say, the management of diabetes where blood sugar has been measured, in HF there has not been a direct measurement of volume derangement before this diagnostic was developed.”

“In each study, we compared blood volume analysis to a surrogate marker to understand the best way to treat heart failure and, in one study, heart failure with accompanying kidney disease. Both studies demonstrated that accurate blood volume measurement provided important information for physicians to better treat individual cases of fluid overload and potentially reduce additional complications,” said Dr. Wayne L. Miller of Department of Cardiovascular Medicine, Mayo Clinic, who was the lead author of both studies. “Both of these posters underscore the value of accurate blood volume measurement as a means of reducing mortality in this complex to treat patient population.”

One poster, “Volume and Pressure in Heart Failure – Complementary, But Not Two Sides of the Same Coin,” showed the distinction between blood volume analysis and cardiac volume pressure (CVP), which is a surrogate marker for fluid volume expansion and overload in heart failure patients. The study concluded that while both demonstrate value, there is no substitute for clear measurement of fluid volume, as CVP does not accurately reflect volume status and therefore should be an additional measure to blood volume analysis rather than a substitute when making treatment decisions in heart failure patients with potential volume overload. The second poster, “Volume-Kidney Interaction in Chronic Heart Failure – Impact of Subclinical Volume Expansion and Chronic Kidney Disease on Clinical Outcomes,” showed that blood volume has a direct connection with kidney function, demonstrating additional risk in patients with both heart failure and impaired kidneys. Use of the BVA-100 provided investigators with accurate plasma volume measurement in order to assess total risk.